Aryl nitro ethers



United States Patent AERYL NI'IRO ETHERS Edward B. Hodge, Terre Haute,Ind., assignor to Commercial Solvents Corporation, Terre Haute, Ind., acorporation of Maryland No Drawing. Application August 19, 1957 SerialNo. 679,111

9 Claims. (Cl. 260'611) NO: H H NO:

. X where R is alkyl, R is selected from the group consisting of aryland substituted aryl; and X is hydrogen or halogen.

This is a continuation-in-part of my copending application Serial No.630,084, filed December 24, 1956, and now abandoned.

The method of preparing aryl nitro ethers generally used in the industryis described in US. Patent 2,562,151 which consists essentially offorming an aqueous mixture of an alkali base and a primary alcohol,adding an aryl nitroolefin to form an alkali salt of a nitro ether, andhalogenating the mixture to produce the haloaryl nitro ether. Onlyunsymmetrical halogenated aryl nitro ethers can be prepared using thisprocedure; a fact which greatly handicaps the industry in its search forbetter insecticides and pharmaceuticals.

I have discovered that symmetrical aryl nitro ethers can be formed withease by the process of my invention.

which consists essentially of reacting an aryl nitroolefin in a reactionmixture of an alkali base and a N,N-dialkyl lower aliphatic amide,hydrolyzing the alkali salt of the nitro ether, and separating thedesired nitro ether from the reaction mixture. If a halogenated other isdesired, the alkali salt may be halogenated by means known to the art.

The aryl nitroolefins which I employ have the structural formula where Ris aryl and R is alkyl. Typical aryl nitroolefins which can he used inmy process include 2-nitro-1-phenyll-propene, 2-nitro-l-phenyl-l-butene,2-nitro-1-(p-chlorophenyl) -l-bntene, 2-nitro-l-(p-bromophenyl)-l-butene, 2-nitro-1-p-tolyl-l-butene, 2-nitro-l-phenyl-l-hexene, andZ-niti'o-l-(2,4-dichlorophenyl) -l-propene. N,N-dialkyl lower aliphaticamides which can be used as solvents in the production of my nitroethers include amides, such as N,N-dimethylformamide,N,N-dimethylacetamide, N,N- dimethylpropionamide, N,N-diethylacetamide,N,N-dipropylformamide, etc. Any alkali or alkaline earth metal base maybe used in my process; however, I prefer to use potassium or sodiumhydroxide.

According to the process of my invention, an alkali base is reacted withan aryl nitroolefin, in the presence of a dialkyl aliphatic amide. Iprefer to mix the alkali base with the dialkyl aliphatic amide at roomtemperature and then to slowly introduce any desired aryl nitroolefininto the reaction mixture to form an alkali salt of a symmetrical nitroether. In producing my new compounds, it is sometimes necessary to heatthe solution in the solvent.

2 with constant agitation in order to dissolve the nitroolefinSimilarly, the nitroolefin can be dissolved in some instances it it isadded in small amounts with constant agitation.

' Following production of the alkali salt of the symmetrical nitroether, I then treat the salt with a weak acid in order to obtain thedesired aryl nitro ether. Suitable acids include dilute solutions ofnon-oxidizing mineral acids or weak organic acids such as acetic acid.The aryl nitro ether obtained upon hydrolysis is insoluble in thesolvents employed and consequently precipitates and is easily recovered.

. If a symmetrical dihalo aryl nitro ether is desired, the alkali saltof the aryl nitro ether can be halogenated by use of agents suitable forhalogenation of aliphatic hydrocarbons providing such agents are notadversely afiected by nitro groups. I prefer to halogenate the alkalisalts of the aryl nitro ethers of my invention by the introduction offree halogen into the reaction mixture resulting from reaction of thealkali base with the aryl nitroolefin.

The proportions of the reactants used are not critical; excellentresults are obtained with equimolar amounts of the reactants. Theprocess of my invention can be carried out at any temperature within therange from 0 to 70 0.; however, I prefer to carry out the process at atemperature of about 20-30 C.

The following specific examples will further illustrate my invention,but it is not intended that my invention be limited to the specificamounts, procedures or proportions set forth therein.

" mole) and mls. of dimethylacetamide, 19.7 grams of2-nitro-1-(p-chlorophenyl)-l-propene (0.1 mole) was incrementallyintroduced with constant stirring. After the olefin was completelystirred into the solution, the reaction mixture was acidified withacetic acid to precipitate white crystallinebis[2-nitro-l-(p-chlorophenyl)propyllether. After recrystallization fromcyclohexane and benzene, 3.3 grams of bis[2-nitro-l-(p-chlorophenyl)-propyllether was recovered having a melting point of l7l-l73 C.

- EXAMPLE II EXAMPLE III To 200 mls. of dimethylformamide was added 32.6grams of Z-nitro-I-phenyl-l-propene and 9 grams of sodium hydroxide in50 mls. of Water. To this reaction mixture, 10 mls. of bromine wereadded dropwise at 20 C. forming a two-layer mixture. From the lowerlayer, white crystalline bis(2-nitro-2-bromo-1-phenylpropyl)ether slowlyprecipitated. On recrystallization from ethyl alcohol, 8.6 grams ofproduct was obtained having a melting point of 148149 C.

EXAMPLE IV Utilizing the procedures of the above examples, the followingethers were prepared using the indicated reactants.

Table I Halogen Solvent Base O-lefin Product N,N-dimethy1-propi0namidePotassium Hydroxide." 2 Nitro 1 (2,4 Dichloro Bis [2 Nitro 1 (2,4dichlorophenyl) phenyD-l-propene. propyl] ether.

N,N-dimethy1 iormamide Barium Hydroxide 2-Nitro-l-phenyl-l-butene B is-(2-nltro-1-phenylbutyl) ether. N,N-Dimethyl-acetamide Sodium Hydroxide2-Nitro-1-p-tolyl-l-propene Bis-(2-nitro-l-ptolylpropyl) ether. N,N-Diethyl-acetamide do 2-Nitro-1-phenyl-LhexenaBis-(2-nitro-1-phenylhexyl) ether.

Chlorine do do 2-Nltro-1-pheny1-1bntene Blst-h(2-nitro-2-chloro-l-phenylbutyl) e er.

EXAMPLE V The bacteriostatic activity of my new compounds was determinedin vitro by the following test. Stock solutions of my novel aryl nitroethers in acetone were prepared containing 10,000 meg/ml. These stocksolutions were then diluted to desired test concentrations usingdistilled water and North Gelatin Agar (Difco), The pH of the dilutedsolutions was adjusted to 7.3. A series of slants of the same mediumwere prepared and streaked with a representative series ofmicroorganisms. Results were recorded after 24 hours incubation at 37 C.

where R and R have the same meaning as above, with an alkali base in thepresence of a N,N-dialkyl alkylamide, and subjecting the reactionproduct to acid treatment to obtain an aryl nitro ether.

8. A recess for the reduction of com ounds havin Growth of the organismson control plates reached a maxih p p P g t e structural formula. mum,for recording purposes, at th1s tune.

The following table discloses the amounts of two rep- Y H Y resentativeethers required to achieve partial and complete RC O CR bacteriostasis.1 I u Minimal Inhib. 00110., ug/ml.

Bis (2-bromo-2-nitro- Bis[2-bromo-2-nitrol-phenylpropyl)l-(p-chlorophenyl) ether propyl] ether Partial Complete Partial Complete150.21 Micrococcus pg ogenes var. attreus 750 1. 500 750 1, 000 160,11Streptococcus faecalis 750 1,500 500 ,000 160.22 Streptococcushemolyticus 750 1, 500 500 1, 000 225.11 Escherichia coli 1, 500 1, 500750 1, 500 245.31 Pasteurella pseudotuberculo 500 1, 000 250 1, 000270.11 ShzgeZla dysenteriae 1, 500 1,500 750 1, 500 800.21 Mycobacteriumranae 1, 500 1, 500 250 750 Now having described my invention, what Iclaim is: 1. A compound having the structural formula:

wherein X is halogen, R is lower alkyl and R is a radical selected fromthe group consisting of phenyl, lower alkyl substituted phenyl, andhalogen substituted phenyl, which comprises reacting an olefin havingthe structural formula:

1'1 N0 R -o=( J-R H,

where R and R have the meaning given above, with an alkali base in thepresence of a N,N-dialkyl alkylamide, and halogenating the reactionmixture.

9. The process of claim 8 in which the halogenating agent is a molecularhalogen.

References Cited in the file of this patent UNITED STATES PATENTS SenkusOct. 25, 1949 Senkus July 24, 1951

1. A COMPOUND HAVING THE STRUCTURAL FORMULA: